(Stroke. 2000;31:2011.)
© 2000 American Heart Association, Inc.
Special Report |
Posterior Circulation Ischemia: Then, Now, and Tomorrow
The Thomas Willis Lecture—2000
Presented as the Thomas Willis Lecture at the American Heart Association 25th International Stroke Conference, New Orleans, La, February 10, 2000.
From the Department of Neurology, Beth Israel Deaconess Medical Center, Boston, Mass.
Correspondence to Louis Caplan, MD, Department of Neurology, Dana 779, Beth Israel Deaconess Medical Center, 330 Brookline Ave, Boston, MA 02215. E-mail lcaplan{at}caregroup.harvard.edu
Key Words: basilar artery • cerebral embolism • cerebral infarction • vertebral artery • vertebrobasilar circulation
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Introduction |
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 Top Introduction Development of IdeasTreatment1960 to Mid 1980sPosterior Circulation Disease:...NEMC Posterior Circulation...Now and the FutureReferences |
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To know and appreciate where we are now and where we are going in the future, it is essential to know where we have been. We cannot afford to relive and repeat the history of stroke every several decades. Posterior circulation stroke represents a microcosm of stroke in general. In this presentation I first review the development of ideas regarding brain and posterior circulation ischemia and its recognition and treatment. I then share some recent data from a large prospective registry of patients with posterior circulation ischemia. Finally, I look ahead to reflect on what I believe should be the future directions for research and for the care of patients with posterior circulation disease.
Patients who present to physicians and hospitals with symptoms that suggest posterior circulation ischemia are handled differently from patients who have symptoms that suggest anterior circulation disease in the great majority of medical facilities in the United States and in the world. A patient who has an attack of dizziness with diplopia and ataxic gait usually has a brain image but seldom has vascular or cardiac investigations. A diagnosis of "vertebrobasilar insufficiency" (VBI) is often made, and physicians then debate whether or not to treat with warfarin-type anticoagulants, and, if so, for how long and at what intensity. In contrast, a patient who has right-hand weakness and aphasia is usually evaluated and treated quite differently at the very same facilities. Brain imaging, cardiac investigations, noninvasive vascular tests of the carotid and intracranial anterior circulation with the use of extracranial and transcranial ultrasound and/or MR angiography (MRA) and CT angiography, and catheter angiography are often pursued, depending on the local technological capabilities and experience of the treating physicians. An effort is made to identify the etiology and mechanism of the ischemia. Treatment is then chosen among a variety of possibilities (including carotid artery surgery, angioplasty, anticoagulants, and antiplatelet aggregants) depending on the nature, location, and severity of the occlusive disease and the mechanism of ischemia.
Why should anterior and posterior circulation ischemia be handled so differently? Does this schizophrenic approach make sense? After all, the internal carotid artery and its branches and the vertebral (VA) and basilar arteries (BA) and their branches are just a few inches apart; they are made of the same coats and look the same under the microscope except for size. These vessels carry the same blood under the same blood pressure. The diseases that affect the blood vessels in the 2 circulations are the same. Do stroke mechanisms really differ between the 2 circulations? How did this differing approach originate, and does it continue to make sense today? These are some questions that I will attempt to answer as I review the development of ideas about posterior circulation ischemia and as I report recent data.
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Development of Ideas |
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TopIntroductionDevelopment of IdeasTreatment1960 to Mid 1980sPosterior Circulation Disease:...NEMC Posterior Circulation...Now and the FutureReferences |
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Herein I review how knowledge about the posterior circulation evolved. To be as concise as possible, I have eclectically selected key individuals and their contributions. I was fortunate to have been mentored by some of the individuals who have made key contributions during the second half of the 20th century.
Clinicoanatomic Correlations
The first important question that physicians asked concerned the
anatomy of the brain. What did the brain look like? How did it
work? Which areas were responsible for which functions? One of the very
first important observers was Sir Thomas Willis. Willis
(1621–1675) was born soon after the deaths of
Shakespeare and Queen Elizabeth. Great Britain was still basking in the
artistic and cultural bloom of Elizabethan England. Willis was a very
successful practicing physician and an accomplished organizer, teacher,
and researcher. He performed necropsies on his patients and did
extensive anatomic dissections, especially on the brain. His coworkers
included the physicists Robert Hooke and Robert Boyle; Richard Lower,
an anatomist, physiologist, and clinician who administered the first
blood transfusion1 ; and Sir Christopher Wrenn, the
renowned architect and artist. Wrenn is responsible for the engraved
plates from which the illustrations in Willis’ The
Anatomy of the Brain and Nerves2 3 are
derived.
Willis became the Sedleian Professor of Natural Philosophy at Oxford University. His anatomy text contains detailed description of the brain stem, the cerebellum, and the ventricles, with extensive hypotheses about the functions of these brain parts. He was the first person to use the term neurology. Willis knew and collaborated with other 17th century giants: Sir Isaac Newton; John Locke, physician and philosopher; and William Harvey.
After Willis, there was a relative lull in activity concerning brain anatomy and function until the latter years of the 19th century, when physicians, mostly in France, Germany, and the United Kingdom, reported case studies of patients that helped to elucidate the anatomy and functioning of the brain stem. The so-called classic brain stem syndromes, all eponymic and named after the original describers of the syndromes, were stimulated by a fascination of the authors with the anatomy and functions of the brain stem.4 We still recognize today these various constellations of findings as the midbrain syndromes of the following: Weber4 5 (ipsilateral third nerve paresis and contralateral hemiparesis); Benedikt4 6 7 8 (ipsilateral third nerve paresis and contralateral hemiparesis, tremor, and involuntary movements); Claude8 9 10 (ipsilateral third nerve paresis and contralateral limb ataxia with gait ataxia); the pontine syndromes of Millard-Gubler11 12 (ipsilateral facial palsy and contralateral hemiparesis) and Foville13 (ipsilateral facial palsy and conjugate gaze paresis with contralateral hemiplegia); the medullary syndromes of Wallenberg14 15 (lateral medullary syndrome) and Babinski-Nageotte16 (lateral medullary syndrome with a contralateral hemiparesis); and the thalamic syndrome of Dejerine-Roussy17 (contralateral hemisensory loss with contralateral ataxia and clumsiness and delayed onset of pain). Many of the lesions described in these reports were not vascular in etiology; some were tuberculomas, tumors, and focal infections. Although most reports were single necropsy-based case reports, some had no necropsy confirmation. Wallenberg’s reports were particularly exemplary. He reported detailed clinical findings, predicted the location of the medullary lesion, and then later described the necropsy findings.14 15
The next important contributor was Joseph Jules Dejerine (1849–1917).
Dejerine was a master clinician and anatomist.18 19 He was
a large man who created an imposing image on ward rounds (Figure 1
). Dejerine was associated with the
Salpetriere and Bicetre hospitals in Paris, and in 1910 he assumed the
Charcot chair. His wife, Augusta Klumpke, was an accomplished clinician
and artist.20 She is responsible for the elegant
illustrations in Dejerine’s 2 major contributions: his
anatomy21 and semiology22 texts.
Dejerine and Dejerine-Klumpke drew illustrative cartoons that depicted
the symptoms and signs in patients with various brain stem and cerebral
lesions. Figure 2 shows one of the
cartoons depicting the anatomy and findings in a patient with a
hemimedullary infarct. Dejerine described the findings in patients with
different varieties of reading abnormalities and first described the
syndrome of alexia without agraphia.23
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Charles Foix (1882–1927) was probably the first modern stroke neurologist. Foix was born in Salies-de-Bearn, a small village in southern France.24 25 He spent his entire medical career within the hospital systems of Paris (Hotel Dieu, Necker, Bicetre, Salpetriere). He was a clinician, anatomist, revered teacher, writer, and poet. Within a 3-year period (1924–1927), he and his coworkers published an astonishing array of reports concerning the clinicoanatomic correlation of symptoms and signs with softenings at various sites in the cerebral hemispheres and the brain stem.26 Especially important in relation to posterior circulation disease were his studies of the thalamic syndromes,27 syndromes related to occlusions of the posterior cerebral arteries,28 and the lateral medullary syndrome.29
Later clinicians clarified the clinical findings in patients with pontine infarction related to basilar artery occlusion30 ; patients with cerebellar infarction at various loci in the cerebellum31 32 33 34 35 ; midbrain, thalamic, and occipital and temporal lobe infarction in patients with embolism to the "top-of-the-basilar" artery35 36 ; and patients with small localized infarcts in the pons, medulla, and thalamus caused by disease of the penetrating artery supply.35 37 38 39 40 41 42 43 44 45 46
Vascular Anatomy
Concurrent with the interest in how the brain looked and how it
worked was an interest in how the different parts of the brain were
supplied with blood. Thomas Willis was probably the first to study
the circulatory supply of the brain in detail. He wrote the following
about the anatomy of the vertebral circulation:
as the Carotides carry the tribute of the blood to the brain; so the Vertebrals serve chiefly for watering the cerebellum and the hinder part of the oblong marrow. . . . The Vertebral Artery passes through little holes cut in the extuberances of the Vertebrae till it comes near the base of the skull and is admitted through the last hole. . . . Beneith the Cerebellum the Vertebral branches are united.2
Willis is usually remembered as the describer of the
vascular composition of the large arteries at the base of the brain,
the so-called circle of Willis. He emphasized the capability for
collateral circulation if an artery became blocked and the
interconnection of blood vessels (Figure 3). A section in his anatomy text
is devoted to "for what use the wonderful net is made, and the reason
for it."2
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Charles Foix and his colleagues dissected and described in detail the
arteries of both the anterior and the posterior circulation. They
described the arterial supply of the
thalamus,27 47 the posterior cerebral artery and its
branches,28 and the blood supply of the
pons48 49 and the medulla oblongata.29
Especially important was the description of the pattern of blood supply
of the pons (Figure 4).48 49
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The pattern of large median arteries, smaller paramedian arteries, and circumferential arteries is a model for the circulatory supply of the brain stem and also the cerebral hemispheres. Foix also analyzed the clinical findings expected in case of occlusion of the various pontine penetrating and circumferential supply arteries.49
Duret50 51 and Duvernoy52 in France, Stopford53 in England, and Gillilan54 and Stephens and Stilwell55 in the United States were also important contributors to knowledge of the arterial and venous anatomy of the posterior circulation.
Vascular Pathology and the Mechanism of Brain Infarction
During the first half of the 19th century, the terms
encephalomalacia, softenings, and
ramollissements were in general use. These were all
descriptive terms and did not indicate etiology. Not until the
observations of Rudolf Virchow (1821–1902) was it established that
arterial occlusions and diminished blood flow to brain
regions were the cause of softenings and that these lesions were
infarctions. Laennec had already used the term infarction
for pulmonary apoplectic lesions.56 In 1846,
Virchow performed 76 necropsies and found blood clots in 18
peripheral veins and 11 pulmonary
arteries.56 57 He concluded that the blood stream allowed
transport of venous coagula for distances from their origins. He then
described necropsy material in which thrombi originating in the left
atria or cardiac valves blocked cerebral, splenic, and renal arteries.
In animals, Virchow showed that foreign materials placed into the
jugular vein traveled to the lungs and foreign materials placed in
arteries also traveled to distant arterial
sites.56 57 58 Virchow showed that thrombi that formed
within arteries were often caused by lesions of the
arterial wall. Before his work, blockage of arteries was
usually attributed to inflammation. Virchow introduced the terms
thrombus, thrombosis, embolus, and
embolism and deduced the general principles of thrombosis
and embolism.56 Virchow’s triad explained localized
thrombus formation and consisted of the following: (1) an abnormality
of the intima and vascular wall, (2) an abnormality of blood flow,
and (3) an abnormality of blood coagulability. Virchow’s
pathological studies revolutionized thinking about brain infarction,
thrombosis, and embolism.
The early studies of Charles Foix related strictly to the localization of ramollissements (brain softenings) and their vascular supply and accompanying clinical findings. He and his predecessors had shown little interest in the nature and mechanisms of the vascular occlusive process. Several weeks before his death (Foix died at the age of 45 years, likely of a ruptured appendix), Foix and his colleagues Hillemand and Ley delivered a paper at a meeting of the Medical Society of the Hospitals of Paris concerning a study that they performed on the arteries that led to brain infarcts. Although an abstract of this report was published,59 a full article never appeared.
Among 56 brains with infarcts, the artery supplying the infarcts was totally occluded in only 12 and subtotally in 14. In 30 patients the arteries were open. Foix and his colleagues speculated on possible explanations of the arterial patency: (1) arterial occlusion might follow softenings, (2) embolism with distal passage before necropsy, (3) insufficiency (l’insuffisance arterielle), that is, more proximally located circulatory failure, and (4) vasospasm (spasme arterielle).
The next important contributor was Raymond Adams, a neuropathologist
and clinical neurologist. With Charles Kubik, then director of the
neuropathology laboratory at the Massachusetts General Hospital (MGH),
Adams, who at the time was director of the neuropathology laboratory
at the Mallory Institute of the Boston City Hospital, described the
clinical and necropsy findings in 18 patients who at necropsy had
occlusion of the basilar artery.30 Eleven occlusions were
thought to arise in situ, while 7 were considered embolic. Adams and
Kubik described the clinical findings and diagrammed in each case the
location of the arterial occlusion and the resulting brain
stem and cerebellar infarcts (Figure 5). They noted morphological
distinctions between thrombosis and embolism, as follows:
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Thrombosis of the basilar artery could usually be recognized at a glance. The thrombosed portion of the vessel was distended, firm, and rigid and the thrombus could not be displaced by pressure. . . . In embolism, the embolus was usually lodged in the distal portion of the basilar artery.30
Thrombosis was engrafted on arteriosclerotic lesions, while a displaceable embolus often blocked a normal-appearing artery. Thrombosis was often superimposed on emboli distally and/or proximally.30 Adams later became chairman of the Neurology Department at MGH, where he and his protege Charles Miller Fisher performed many important clinical and pathology studies of various stroke conditions.
C. Miller Fisher is the individual probably most responsible for furthering information about stroke and stroke mechanisms during the 20th century. Fisher, a Canadian by birth, came to the Boston City Hospital and later to MGH to study neuropathology with Raymond Adams. He created the Stroke Service at MGH, the first of its kind in the United States. I was a Stroke Fellow with Dr Fisher in 1969–1970, at which time I also came under the tutelage of Raymond Adams.
Fisher’s 1951 report on occlusion of the internal carotid artery was a benchmark in the history of stroke.60 This article emphasized that occlusions commonly developed in the neck engrafted on atherosclerosis and that transient ischemic attacks (TIAs) often preceded and warned of the ensuing stroke. The carotid artery stenosis was possibly approachable surgically. Before this report, although in 1905 Chiari had described a patient with embolism arising in an occlusion of the internal carotid artery in the neck,61 anterior circulation infarcts were invariably attributed to middle cerebral artery disease. In 1954, Fisher reported subsequent observations on internal carotid artery disease.62 Later Fisher and his colleagues described the distribution of atherosclerotic lesions found at necropsy within the extracranial and intracranial anterior and posterior circulations.63 Within the posterior circulation, Fisher described occlusions of the vertebral artery in the neck64 ; with Kubik and Karnes he described the vascular pathology found at necropsy in patients with lateral medullary infarcts65 and emphasized that intra-arterial embolism ("local embolism") was an important mechanism of stroke in the posterior circulation as well as in the anterior circulation.66 In a series of meticulous analyses of serial sections from patients with small deep infarcts, many located in the brain stem, Fisher described the pathology in the penetrating arteries, lipohyalinosis and atheromatous branch occlusions, that caused penetrating artery territory infarcts.46 67 68 69
Physiology of the Cerebral Circulation
Derek Denny-Brown (1901–1980), a neurophysiologist, introduced
and popularized the term cerebrovascular insufficiency to
explain TIAs and the fluctuating nature of brain ischemia.
Denny-Brown was born in New Zealand and trained there at the University
of Otaga in Duneeden. A Beit Memorial Fellowship allowed him to work in
the neurophysiology laboratory of Sir Charles Sherrington during
1925–1928. In 1928 he became house physician at the National Hospital
Queens Square and St Bartholomew’s Hospital in London. In 1941 he was
appointed to the James Jackson Putnam Chair at the Harvard Neurological
Unit at the Boston City Hospital. Raymond Adams was the
neuropathologist in Denny-Brown’s Neurology Department at the Boston
City Hospital, and Miller Fisher also spent some time there working
with Adams. Denny-Brown was my department chairman and mentor during
1966–1969 during my neurology training on the Harvard Neurological
Unit. I was in the last group of neurology residents that Denny-Brown
trained. Denny-Brown was a physiologist by training. Although he had
assisted in necropsies in the neuropathology laboratory of Godwin
Greenfield at the National Hospital and performed his own staining and
microphotography,70 he considered that physiology was
a dynamic, living discipline that explained many clinical neurological
phenomena better than morphological analyses performed at
necropsy. During the1950s and early 1960s he studied and wrote about
hemodynamic considerations in patients with brain
ischemia in the anterior and posterior
circulations.71 72 73 At that time, "vasospasm" was the
popular explanation for TIAs.
We therefore postulated an explanation alternative to that of vasospasm, namely, a state of carotid insufficiency determined by either stenosis or occlusion of the internal carotid artery, with its vascular territory left supplied by collateral branches. . . . A similar situation in relation to the basilar artery accounted for insufficiency of supply of the brain stem and posterior cerebral artery territory of that artery. On this basis, carotid or basilar insufficiency was a physiological, potential hemodynamic state, in which reversible hemodynamic crises could be elicited by any factor that impaired the collateral circulation.73
Denny-Brown and John Sterling Meyer, his associate, attempted experimentally, using tilt-tables and blood pressure manipulation, to demonstrate the sensitivity of the circulation to hemodynamic perturbations, but, in general, these experiments failed.
At about the same time, clinicians at the Mayo Clinic, Bob Siekert and Clark Millikan, reported a series of patients who had fluctuating symptoms affecting brain structures supplied by the posterior circulation arteries that they termed VBI.74 Siekert later served during 1976–1981 as the first program chair of the International Stroke meeting of the American Heart Association.75 Other clinicians, including Fang and Palmer in California76 and Denis Williams in the United Kingdom,77 78 wrote about symptoms and signs in patients with VBI, and the term became popular on both sides of the Atlantic Ocean.
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Treatment |
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TopIntroductionDevelopment of IdeasTreatment1960 to Mid 1980sPosterior Circulation Disease:...NEMC Posterior Circulation...Now and the FutureReferences |
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During the first half of the 20th century, there was little interest among neurologists in active treatment, other than rehabilitation, of patients with strokes. During the 1950s and 1960s, anticoagulants of the heparin and warfarin types were being used to treat patients with myocardial infarction and pulmonary embolism. Although Craven79 80 had written about anticoagulant effects of aspirin, it was not yet used extensively. During this time, reports from the Mayo Clinic stroke service (Millikan, Siekert, and Whisnant) enthusiastically endorsed anticoagulant treatment of posterior circulation vascular disease (VBI).81 82 83 Millikan et al81 first described 21 patients with progressing vertebrobasilar territory strokes who were treated with anticoagulants. Only 3 (14%) died compared with 10 of 23 deaths (43%) in a retrospective search for similar patients not anticoagulated. Attacks stopped in all 5 patients who had VBI spells. Later Whisnant described the results among 140 patients with progressive posterior circulation ischemia.83 Twelve (8.5%) died compared with 23 of 39 deaths (59%) in similar patients not anticoagulated. VBI attacks often stopped after anticoagulation.
Although these studies were retrospective and uncontrolled and the causative vascular lesions were most often not studied, anticoagulants were widely accepted as the proven treatment for patients with vertebrobasilar territory ischemia. After all, the prevailing view at that time, from the report of Kubik and Adams30 and others, was that VBI was nearly always fatal or disabling. The fact that most of the anticoagulant-treated Mayo Clinic patients survived, many without major neurological deficits, and attacks of brain stem and cerebellar ischemia stopped was considered persuasive by clinicians.
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1960 to Mid 1980s |
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TopIntroductionDevelopment of IdeasTreatment1960 to Mid 1980sPosterior Circulation Disease:...NEMC Posterior Circulation...Now and the FutureReferences |
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After Fisher’s reports on carotid artery disease,60 62 angiography was widely used to detect extracranial vascular disease, and surgical carotid endarterectomy became popular. With the introduction of CT in the 1970s and more widespread use of extracranial ultrasound, patients with anterior circulation ischemia were usually investigated for the causative vascular lesions and stroke mechanisms. Various etiologies and mechanisms were defined, including the following: internal carotid artery disease in the neck (plaques, stenosis, or occlusion), intracranial internal carotid artery stenosis and occlusion, cardiogenic embolism, middle cerebral artery and anterior cerebral and anterior choroidal artery occlusive lesions, and penetrating artery disease with lacunar infarctions. The term carotid insufficiency was abandoned. Various treatments were used, depending on the nature and severity of the vascular lesions found. Popular treatments included aspirin, other platelet antiaggregants, anticoagulants, neck surgery, and extracranial-to-intracranial bypass surgery.
Although angiography was widely used in patients with anterior circulation disease, it was considered risky in patients with posterior circulation disease. Early-generation CT scans were ineffective in showing brain stem and cerebellar infarcts, and ultrasound was rarely used to study the vertebral arteries. Cardiogenic embolism was considered a rare cause of posterior circulation ischemia. Patients with posterior circulation ischemia were classified as having VBI and seldom had cardiac and vascular testing. Therapeutic debate centered solely around anticoagulation.
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Posterior Circulation Disease: 1985 to the Present |
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The past 15 years have seen a technological revolution. The advent of MRI, with its ability to better image posterior fossa structures, made investigation of vertebrobasilar territory infarcts more feasible. Transcranial Doppler ultrasound (TCD) and MRA provided methods of studying the vertebral and basilar arteries safely and quickly. Extracranial ultrasound was more often used, especially in Europe, to define lesions within the extracranial subclavian arteries and the vertebral arteries. Cardiac investigations also improved with better echocardiography, which showed lesions in the aorta as well as the heart. It became possible to investigate the brain and cardiovascular lesions and stroke mechanisms quickly and noninvasively in patients with posterior circulation ischemia. During this time a number of other treatments—surgery on the extracranial vertebral arteries (ECVA), extracranial and intracranial angioplasty, newer antiplatelet aggregants, and thrombolysis—were introduced and applied to patients with posterior circulation ischemia.
I have always advocated thorough investigation of patients with both anterior and posterior circulation ischemia.35 84 85 86 87 Beginning in 1988, when the technology became available, my colleagues Michael Pessin and Dana DeWitt and I, together with our stroke fellows, began to prospectively collect data in a computerized registry on all of our personally examined patients with posterior circulation strokes and TIAs. The New England Medical Center (NEMC) Posterior Circulation Registry was continued until 1996 and accumulated 407 patients. The clinical data and imaging studies on each patient were reviewed on multiple occasions, and a consensus of the findings and stroke mechanisms was made. The diagnostic criteria and a review of the results among the first 300 patients have been published.35
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NEMC Posterior Circulation Registry Results |
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TopIntroductionDevelopment of IdeasTreatment1960 to Mid 1980sPosterior Circulation Disease:...NEMC Posterior Circulation...Now and the FutureReferences |
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Investigations
All patients were thoroughly investigated. All had brain imaging (CT or MRI); >80% had MRI. All had vascular imaging (MRA, angiography, or TCD). Most patients had catheter angiography, nearly all in the early years but fewer as the diagnostic quality of MRA improved. Most patients had extracranial ultrasound and TCD of the posterior circulation arteries, and many had echocardiography and cardiac rhythm monitoring.
Distribution of Brain Infarcts
To describe the location of infarcts, we subdivided the posterior
circulation into proximal, middle, and distal intracranial territories.
The proximal intracranial posterior circulation territory included
regions supplied by the intracranial vertebral arteries (ICVA): the
medulla oblongata and the posterior inferior cerebellar
artery (PICA)–supplied cerebellum. The middle intracranial posterior
circulation territory included the brain supplied by the basilar artery
up to its superior cerebellar artery (SCA) branches: the pons and the
anterior inferior cerebellar artery (AICA)–supplied
cerebellum. The distal intracranial posterior circulation territory
included all the territory supplied by the rostral basilar artery,
SCAs, and the the posterior cerebral arteries (PCAs), and the
penetrating branches of these arteries to the midbrain and thalamus.
These subdivisions are shown diagrammatically in Figure 6, modeled after a figure in the Duvernoy
atlas.52 The location of infarcts within the cerebellum is
particularly useful in localizing the rostrocaudal location of
infarction. The cerebellar blood supply is shown in Figure 7.
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We used both clinical and imaging data to localize infarcts. For
example, if a patient had a lateral medullary syndrome and a hemianopia
on examination, but MRI showed only a lateral medullary infarct, the
patient was classified as having both proximal and distal territory
infarcts. Infarcts were localizable in 347 of 407 patients (85.3%).
The others had either repeated TIAs or persistent deficits that could
not be definitively localized clinically or by brain imaging. The
frequency of the brain locations of these 347 infarcts is shown in
Table 1. The table notes those
patients in whom proximal, middle, and distal territory segments were
included as well as the specific locations, eg, proximal only, middle
and distal, and proximal and distal. The most common location of
infarcts was in the distal segment. Distal+ infarcts (ie, infarcts in
the distal territory and also in other territories) were especially
common.
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Stroke Mechanisms
The distribution of stroke mechanisms among the registry of 407
patients is shown in Table 2. This table
shows the single most likely diagnoses and also the range of diagnoses
thought plausible. For example, in the first column embolism of cardiac
origin was listed only when it was considered the most likely
mechanism, but in the second column all patients with a potential
cardiac embolic source were included. The most common stroke mechanism
was embolism. The most common donor sources were the heart and
vertebral arteries. Table 3 shows
the localization of infarcts in patients in whom the single most likely
stroke mechanism was embolism. Embolism caused mostly distal, proximal,
and proximal and distal territory infarcts. The most common recipient
arteries in patients with embolism were the ICVA and its PICA branches
and the distal basilar artery and its SCA and PCA branches. Figure 8 shows the usual loci of embolism.
Cardiogenic embolism was more likely to cause distal territory
infarcts, while intra-arterial embolism from the ECVA more
often caused proximal and proximal and distal territory infarcts. PICA
cerebellar and PCA territory infarcts were especially common in
patients with cardiogenic embolism. The large-artery disease category
was used to describe patients who had severe stenosis or
occlusion of 1 or more large extracranial or intracranial arteries in
whom a hemodynamic mechanism was considered the
explanation for low perfusion infarcts or repeated TIAs. These patients
usually had infarcts in the brain stem in the center of the supply zone
of an occluded ICVA or basilar artery or had multiple large-artery
occlusive vascular lesions and multiple TIAs, often posturally
related.
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Vascular Occlusive Lesions
The distribution of vascular occlusive lesions (those arteries
with >50% stenosis) is noted in Table 4. The most common site of
occlusion was the ECVA, mostly involving the origin of the artery from
the parent subclavian artery. Intracranial occlusive disease was also
very common and involved the ICVA and basilar arteries about equally.
Innominate and subclavian artery diseases were rare among patients with
symptomatic posterior circulation infarcts.
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We analyzed and reported the findings among the 80 patients in
the registry who had severe occlusive disease (>75% stenosis
or occlusion) of the ECVA in its first segment (between the origin of
the artery and penetration into the vertebral column).88
The great majority of the occlusive lesions, 73 (91%), were due
to atherosclerosis, while 6 patients had dissections,
and 1 patient had a large aneurysm of the proximal ECVA caused
by previous insertion of a jugular line into the artery. ECVA disease
was often accompanied by intracranial occlusive disease. Among the 80
patients, there were 37 occlusions, 34 stenoses, and 12
bilateral occlusive lesions. Risk factors in those with
atherosclerosis were identical to those usually found
in patients with internal carotid artery origin disease: smoking,
hypertension, and coronary artery disease. There were 2
patterns of symptoms in patients with ECVA occlusive disease. Some
patients had TIAs, usually brief and multiple during a short period of
time (days or weeks) and sometimes precipitated by changes in position.
Symptoms during the attacks were usually described as dizziness,
vertigo, veering or listing to the side, visual blurring, and diplopia,
indicating vestibulocerebellar system ischemia. Many patients
had sudden-onset strokes, most often involving the PICA-supplied region
of the cerebellum or involving the distal intracranial territory. In
some patients TIAs were followed by sudden-onset strokes. The most
common mechanism of stroke in patients with ECVA artery disease was
intra-arterial embolism. Only 13 patients had only TIAs,
among whom 12 had bilateral severe ECVA stenosis or occlusion.
The 13th patient had bilateral internal carotid artery occlusion and
unilateral severe ECVA disease.88 Angiography often showed
occlusion of the ECVA at its origin, with well-developed collateral
circulation from the external carotid and the thyrocervical and
costocervical arteries (Figure 9). ECVA
surgery can be performed safely by surgeons experienced in the
procedure,89 but we still do not know which patients are
surgical candidates. Angioplasty is also possible, but indications,
risks, and benefits have not been studied.
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Severe occlusive disease of the ICVA most often affected the distal portion of the artery beyond the PICA branch and often near the ICVA-BA junction.35 90 91 92 Unilateral vertebral artery occlusive disease was unusual; most patients had either bilateral severe occlusive disease or unilateral ICVA disease, and occlusive disease or hypoplasia of the contralateral ECVA, ICVA, or basilar artery or the contralateral ICVA ended in PICA. Concurrent stenosis of the basilar artery was quite common. The ICVA was a common recipient site and donor source for embolism. Embolism to the ICVA (most often from the heart or ECVA) caused predominantly PICA-cerebellar infarcts. Embolism from the ICVA caused distal territory infarcts usually involving the SCA and/or PCA territories. To our surprise, ICVA occlusive disease most often did not cause infarcts limited to the proximal intracranial territory. Only 14 patients (19%) with severe ICVA disease had infarcts limited to the medulla or PICA cerebellum.90 This is explained by the predominant location of occlusive disease within the ICVA beyond the PICA branches. The 2 most common groups of patients with ICVA disease had embolism to the distal territory from the ICVA (32%) and multifocal TIAs in patients with extensive occlusive disease, usually involving both the ICVA and often the basilar artery as well (52%).90 The patients with extensive ICVA and basilar artery disease had surprisingly good outcomes. Most had positionally related TIAs but seldom had disabling strokes. Patients with embolism to and from the ICVA had worse outcomes than those with the most extensive occlusive disease.
Patients with basilar artery disease often had TIAs preceding strokes.
Neurological symptoms during TIAs were most often motor and
oculomotor.35 As the diagrams of Kubik and Adams (Figure 5
) show, ischemia is predominantly in the paramedian
pontine base and tegmentum, where the pyramidal tracts and
oculomotor structures (sixth nerve nuclei, medial longitudinal
fasciculi, and paramedian pontine reticular formation neurons for
lateral gaze) are located. Collateral circulation from the ICVA and
circumferential cerebellar arteries maintains perfusion of the lateral
structures subserving sensation and vestibulocerebellar functions.
Hemiparesis with slight contralateral motor or reflex abnormalities was
more common in our series than tetraplegia. Thrombosis of the basilar
artery engrafted on atherosclerotic narrowing more often caused
infarction in the caudal and middle pons, while embolism to the basilar
artery caused infarction in the rostral pons, midbrain, and SCA and PCA
territories ("top-of-the-basilar" region). The outcome in patients
with basilar artery disease was surprisingly good and better than
previously reported. Many patients with basilar artery occlusion had no
or minor deficits. Only 1 patient died from the stroke, and only 27
(7.7%) had major disability or death due to basilar artery disease.
Benign outcome is the rule in patients with short-segment occlusions
and those in whom the distal portion of the basilar artery, the main
supply of the tegmentum of the pons, remains open.
The great majority of PCA territory infarcts and PCA occlusions were embolic (65/79, 82%).35 93 Cardiogenic embolism (n=32 [41%]) and embolism from the ECVA, ICVA, and basilar artery (n=25 [32%]) were the most common sources of embolism, while 8 (10%) were categorized as cryptogenic embolism.93 Intrinsic PCA disease was present in only 7 patients (9%). Vasoconstriction due to migraine and coagulopathies accounted for 9% of PCA territory infarcts. Embolism has also been the predominant mechanism of PCA territory infarcts in prior series of patients.94 95 96 97 The most common finding was a hemianopia or other visual field deficit. Patients with hemisensory symptoms had thalamic ischemia in relation to proximal occlusions of the PCA before the thalamogeniculate branches.98 Hemiplegia occurred rarely.
Outcomes
Posterior circulation ischemia had a more benign
outcome in the NEMC registry than previously thought. The outcomes at
30 days in the NEMC Posterior Circulation Registry are shown in Table 5. Most patients (n=284 [78.7%]) had
no or minor disability. Death attributed to cerebrovascular disease was
very rare (1.9%), and total mortality at 30 days was 3.6%. Mortality
and major disability were present in approximately one fifth of
patients (21.3%). Mortality (n=3 [4%] at 3 weeks) was similar in a
series of 70 patients with acute posterior circulation infarcts who had
MRI/MRA in the Lausanne Stroke Registry,99 but others
estimated that >50% of patients with vertebrobasilar territory
ischemia died or became severely disabled.35
Series of patients with poor outcomes invariably selected only patients
with severe neurological signs for angiography and for inclusion in
their series.
|
Table 6 shows death and major
disability at 30 days according to stroke mechanisms. Embolism
(especially cardiogenic embolism) was the major contributor to poor
outcome, as it has been in patients with anterior circulation infarcts.
The poorest outcomes occurred in patients with distal territory
infarcts, especially if both the middle and distal territories were
involved. As expected, basilar artery disease (n=27 [7.7%]) and ICVA
disease (n=19 [5.2%]) were the vascular occlusive lesions that
accounted for most instances of death or major disability.
|
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Now and the Future |
|---|
|
TopIntroductionDevelopment of IdeasTreatment1960 to Mid 1980sPosterior Circulation Disease:...NEMC Posterior Circulation...Now and the FutureReferences |
|---|
Modern technology now allows physicians to quickly and safely localize brain lesions within the posterior circulation and to define the location and severity of occlusive vascular lesions. Diffusion-weighted (DW) images and perfusion-weighted images, along with MRA, have expanded this capability. Figures 10 to 12
show examples of patients with posterior circulation
ischemia in whom these modern MR capabilities clarified the
diagnosis. Figure 10 shows a medullary infarct due to an ICVA
occlusion shown by DW image when T2-weighted images were normal. Figure 11 shows a bilateral vertebral artery dissection shown by MRI.
Figure 12 shows MR images from a patient who had a complex
clinical course with embolism to a dominant ICVA and basilar artery
from an occluded ECVA. Although there is some infarction on DW images
in both proximal and distal territories, the perfusion images show
extensive hypoperfusion in all intracranial territories. This patient
subsequently developed infarction of most of his brain stem and PCA
territories and died.
|
|
|
All patients with brain ischemia, in either the anterior or posterior circulation, deserve full evaluation of their brain and vascular lesions. Brain imaging can now be done with CT or MRI, especially if DW imaging is available. Vascular imaging can be accomplished with CT angiography, MRA, and/or with extracranial and transcranial ultrasound. Cardiac investigations are just as important in patients with posterior circulation ischemia as in patients with anterior circulation ischemia. An important number of posterior circulation infarcts are cardioembolic. Furthermore, brain stem infarcts, especially medullary, can cause cardiac abnormalities. Choice of therapy should be based on the etiologic stroke mechanism; the nature, severity, and location of the vascular lesions; and the extent of brain infarction and hypoperfusion. Once physicians become accustomed to localize and define mechanisms and brain and vascular lesions in patients with posterior circulation ischemia, randomized trials should be designed to study treatment options in patients with various vascular occlusive lesions and stroke mechanisms. Observational studies are also important, especially in conditions in which the number of patients is inadequate for randomized trials. Various treatments, such as platelet antiaggregants, anticoagulants, thrombolytic drugs, surgery, angioplasty, and stents, are possibly effective but depend on the mechanism and vascular lesions responsible for the ischemia.
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Footnotes |
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The opinions expressed in this paper are not necessarily those of the editors or of the American Heart Association.
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References |
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